Abstract: :
Purpose: Recently, Otsuka Long–Evans Tokushima Fatty(OLETF)rat has developed for studying on type 2 diabetes. This studyis to investigate the difference of retinal gene expressionpattern between Otsuka Long–Evans Tokushima Fatty ratsfor type 2 diabetes and Long–Evans Tokushima Otsuka(LETO)rats as normal control using microarray.Methods: The author studied on the retinal gene expression profileof OLETF rats at 18 months and 40 months with microarrays afterthe extraction of retina from OLETF rats and LETO rats. Geneswere sorted into clusters according to their temporal expressionprofiles. They were also grouped according to their potentialpathophysiological significance. Western blot for several geneswas done to verify the microarray results. The rat GeneFiltercontains a total of 1152 genes, of which 1111 genes are knowngenes and the remaining 41 genes are expressed sequence tags(ESTs).Results: At 18 weeks after birth, 53 genes were identified withexpression levels that differed by more than twofold, comparedwith that in control group. The expression of 32 genes wereincreased by twofold or more, whereas expression of 21 geneswere decreased by twofold or more. By 40 week after birth, thenumber of genes displaying more than twofold difference in expressionpattern was increased to 62 genes; 44 genes, elevated levels,18 genes, decreased levels. Genes related to leukocyte adhesion(ICAM–1, endothelial selectin, integrin alpha V), proteinkinase C eta, iota, heat shock protein and nitric oxide synthase3(endothelial cell) were upregulated. However upregulation ofCD44 and downregulation of aquaporin 1 are different from previousreports. Especially upregulation of PDGF beta polypeptide at18 weeks and downregulation at 40 weeks are interesting finding.It may be related to pericyte loss in the early stage of diabeticretina.Conclusions: Nine clusters of genes were identified with verysimilar patterns of expression. This study would suggest thata common regulatory pathway for the genes exist within a cluster,and their identification may provide potential role in new targetsof regulating diabetic retinopathy.